Ken-ichi Asahi

Differentiation of human acute myeloid leukaemia cells in primary culture in response to cotylenin A, a plant growth regulator.

Cotylenin A, which has a diterpenoid tricarbocyclic skeleton, has been isolated as a plant growth regulator, has been shown to affect several physiological processes of higher plants and have differentiation‐inducing activity in several myeloid leukaemia cell lines. We examined the effect of cotylenin A on the differentiation of leukaemic cells that were freshly isolated from acute myeloid leukaemia (AML) patients in primary culture. Cotylenin A significantly stimulated both functional and morphological differentiation of leukaemia cells in 9 out of 12 cases. This differentiation‐inducing activity was more potent than those of all‐trans retinoic acid and 1α,25‐dihydroxyvitamin D3 (VD3). Treatment with a combination of cotylenin A and VD3 was more effective than cotylenin A or VD3 alone at inducing the monocytic differentiation of AML cells.

Treatment of human promyelocytic leukemia in the SCID mouse model with cotylenin A, an inducer of myelomonocytic differentiation of leukemia cells

Cotylenin A has differentiation-inducing activity in human myeloid leukemia cell lines and leukemic cells that were freshly isolated from acute myeloid leukemia (AML) patients in primary culture. Injection of the human promyelocytic leukemia cell line NB4 into SCID mice resulted in the death of all mice due to leukemia. Administration of cotylenin A significantly prolonged the survival of mice inoculated with NB4 cells. In an in vivo analysis, cotylenin A induced the differentiation of leukemia cells in a retinoid-resistant leukemia model. Cotylenin A may be useful for differentiation therapy of retinoid-resistant leukemia.

Induction of the monocytic differentiation of myeloid leukaemia cells by cotylenin A, a plant growth regulator.

Regulators that play an important role in the differentiation and development of plants or invertebrates may also affect the differentiation of human leukaemia cells through a common signal transduction system, and might be clinically useful for treating acute myeloid leukaemia. Cotylenin A has been isolated as a plant growth regulator. We examined the effects of cotylenin A on the differentiation of several myelogenous leukaemia cells, and found that cotylenin A is a potent and novel inducer of the monocytic differentiation of human myeloid leukaemia cells. Cotylenin A induced the functional and morphological differentiation of myeloblastic and promyelocytic leukaemia cells, but did not effectively induce the differentiation of monocytoid leukaemia cells. Cotylenin A‐induced differentiation was not affected by several inhibitors of signal transduction, suggesting that this inducer exhibits a unique mode of action.

Differanisole A, an inducer of the differentiation of Friend leukemic cells, induces stalk cell differentiation in Dictyostelium discoideum

Differanisole A isolated from the conditioned medium of a soil microorganism, Chaetomium strain RB‐001, is an inducer of the differentiation of the Friend leukemic cells (mouse leukemia cells). The chemical structure of this substance is very similar to that of stalk cell differentiation‐inducing factor (DIF) isolated from the cellular slime mould, Dictyostelium discoideum. We examined the effects of differanisole A on Dictyostelium HM44 cells, a mutant strain which is defective in DIF production, and found this substance to be an inducer of stalk cell differentiation in D. discoideum.

Differentiation Inducing Phosphatidyl Choline(s) from the Embryos of Rainbow Trout (Salmo gairdneri): Isolation and Structural Elucidation'

Phospholipid which is able to induce the differentiation of some undifferentiated tumour cells was isolated from the rainbow trout (Salmo gairdneri) embryos.